The Effect of Genetic Variations in the Vitamin D Receptor Gene on the Course of Depressive Symptoms.

BACKGROUND: Evidence on the association between single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and depressive symptoms is inconclusive. OBJECTIVES: The primary aim of the study was to investigate the association between SNPs in the VDR gene and depressive symptoms. METHODS: In a sample of older adults from the Longitudinal Ageing Study Amsterdam (n = 922), depressive symptoms were assessed using the Centre for Epidemiological Studies Depression scale (CES-D scale) at baseline and after 3, 6, and 10 y of follow-up. Blood samples for SNP and serum 25-hydroxyvitamin D3 (25(OH)D3) determination were obtained at baseline. The association between 13 SNPs in the VDR gene and the course of depressive symptoms were evaluated using linear mixed models. The interaction between SNPs and serum 25(OH)D3 in relation to depressive symptoms was evaluated using multiple linear regression. RESULTS: No SNPs were associated with the course of depressive symptoms. Significant interactions between serum 25(OH)D3 and SNPs in the VDR gene were found. Stratified analysis revealed that within the GG genotype strata, 10 nmol/L higher serum 25(OH)D3 was associated with 0.27 (95% CI: -0.50, -0.04) and 0.23 (95% CI: -0.48, 0.02) lower scores on the CES-D scale for Cdx-2 and 1b-G-886A, respectively. This association was not found in persons having the GA or AA genotype. CONCLUSIONS: No SNPs are associated with the course of depressive symptoms. Stratified analysis shows that the effect of serum 25(OH)D3 concentrations on depressive symptoms is different among genotypes of Cdx-2 and 1b-G-886A. Future research should elucidate on the function of Cdx-2 and 1b-G-886A to describe their effect.

Opioids and Falls Risk in Older Adults: A Narrative Review.

Pain treatment is important in older adults but may result in adverse events such as falls. Opioids are effective for nociceptive pain but the evidence for neuropathic pain is weak. Nevertheless, both pain and opioids may increase the risk of falls. This narrative literature review aims to summarize the existing knowledge on the opioid-related fall risk in older adults, including the pharmacokinetics and pharmacodynamics, and assist clinicians in prescribing and deprescribing opioids in older persons. We systematically searched relevant literature on opioid-related fall risk in older adults in PubMed and Scopus in December 2020. We reviewed the literature and evaluated fall-related adverse effects of opioids, explaining how to optimally approach deprescribing of opioids in older adults. Opioid use increases fall risk through drowsiness, (orthostatic) hypotension and also through hyponatremia caused by weak opioids. When prescribing, opioids should be started with low dosages if possible, keeping in mind their metabolic genetic variation. Falls are clinically significant adverse effects of all opioids, and the risk may be dose dependent and highest with strong opioids. The risk is most prominent in older adults prone to falls. To reduce the risk of falls, both pain and the need for opioids should be assessed on a regular basis, and deprescribing or changing to a lower dosage or safer alternative should be considered if the clinical condition allows. Deprescribing should be done by reducing the dosage gradually and by assessing and monitoring the pain and withdrawal symptoms at the same time. Weighing the risks and benefits is necessary before prescribing opioids, especially to older persons at high risk of falls. Clinical decision tools assist prescribers in clinical decisions regarding (de-) prescribing.